The Goal: To improve patient safety and outcomes for all modalities of external-beam radiation therapy in a cost-effective manner by using a new type of HD 3D pre-treatment Patient-Specific Quality Assurance (PSQA). Product to be Developed by the end of Phase II (?The CrystalBall? System?) will consist of a fully robotized fast laser CT of low-cost reusable radiochromic polymer gel dosimeters. It will detect and correct all significant errors accumulated during treatment planning/delivery that would likely be missed by existing QA tools. Existing Paradigms and Clinical Practices Being Challenged: 1) current emphasis on device performance QA rather than process QA; 2) inadequate density of data sampling in measured QA dose distributions in 3D. Health Relatedness of the Project: The ?CrystalBall? will be able to ?predict the future? success or failure of a patient?s radiotherapy treatment. Routine use of this product will lower cancer care costs associated with avoidable recurrences and complications that lead to costly readmissions, disabilities, and premature death. Critical Barrier to Progress in 3D Polymer Gel Dosimetry Being Addressed: Persistent lack of a commercial polymer gel dosimetry package that is not only accurate but also cost-effective and time-efficient. Phase I Specific Aims (Feasibility of Critical Technological Innovations): 1) novel reusable radiochromic polymer gel dosimeter with instant dose response and stable signal, thermally reversible and resettable overnight, suitable for cost-effective daily PSQA usage. Also optically/chemically compatible with selected 3D printing materials; 2) novel design of a cost-effective, fast laser CT scanner for imaging 3D dose distributions in polymer gel dosimeters; 3) novel 3D autocalibration algorithm based on dose-response modeling, enabling a time-efficient single-scan PSQA protocol; 4) novel algorithm for autosegmentation of multi-PTV dose distribution data and for autogeneration of QA reports for individual PTVs, with application to single-isocenter VMAT treatment of multiple brain metastases; 5) novel software interface for HD 3D QA analysis with detailed- analysis options triggered only by suboptimal 3D gamma passing rates and/or other global metrics. [Aims 1, 3, 4 and 5 will be tested at a leading radiation oncology department under a 100% in-kind subcontract]. Outline of Likely Phase II Specific Aims (Continuation of Phase I Research and Product Development): 1) novel fully robotized system for batch-processing all exposed CrystalBalls? for daily PSQA (laser-CT- scanning, QA reports, annealing & resetting overnight); 2) novel designs of phantoms/protocols/software for HD 3D PSQA of SRS, SBRT, VMAT, IGRT, MR-linac, and proton beam therapy, including motion/deformation control and gating; 3) novel design of 3D printed anthropomorphic phantoms compatible with the new polymer gels; 4) novel design of phantoms/protocols/software for HD 3D machine QA (for MLCs, table, gantry, collimator, output); 5) novel software for autogeneration of corrections to treatment plans; 6) novel software for correlating HD 3D QA results with log files, in order to identify likely root causes of detected errors.